Tau protein is a soluble phosphorylated protein present in a state of binding to intracellular microtubules in the normal brain, contributes to the promoted polymerization and stabilization of the microtubules, and maintains an equilibrium state while repeating binding to and dissociation from the microtubules. The break-down of the equilibrium state due to phosphorylation/dephosphorylation enzyme abnormality or the like increases free tau protein in the cytoplasm and leads to the aggregation or fibrosis thereof. In the majority of dementias in elderly people, including Alzheimer's disease and frontotemporal dementia, neurodegenerative diseases in which the accumulation of tau protein aggregates without always the accumulation of amyloid is observed as a characteristic lesion are collectively called tauopathy (Non Patent Literature 1).
In Japan, dementia is seen in about 7% of elderly people 65 or older, and the prevalence reaches about 10% when mild dementia is included. Seventy percent thereof is said to have tauopathy dementia, and the number of the patients is about 2,000,000. In the research and development on dementia, research has previously been ahead on amyloid β (Aβ) protein, a clinical trial using immunization with a peptide from amyloid β has been conducted; however, the trial has been discontinued because meningoencephalitis occurred in 6% of patients inoculated therewith midway through the trial (Non Patent Literature 2). Although the trial has been discontinued, it has been confirmed that the vaccination had the effect of eliminating senile plaques and degenerative nerve projections, from a case report on a patient who developed, and recovered from, encephalitis after the vaccination and then died from another disease (Non Patent Literature 3). The subsequent follow-up study of the vaccinated patient also determined that the disease progressed even in the patient in whom the disappearance of senile plaques was confirmed by autopsy after the vaccination, suggesting that the vaccine had no effect of preventing the progression of the disease (Non Patent Literature 4).
Previous studies have also shown that passive immunity with an antibody to amyloid β is effective; however, the effect of suppressing the progression of the disease has not been elucidated (Non Patent Literature 5).
In addition, the effect of an oral vaccine was tested in which an adeno-associated virus (AAV) vector carried amyloid β. The oral administration of the AAV vector was observed to have the effect of producing an antibody to amyloid β via the intestinal mucosa and the effect of improving a learning function in experiments using mice (Non Patent Literature 6); however, in the subsequent experiment using monkeys, it was observed to decrease senile plaques but was not confirmed to have a definite effect of suppressing the progression of the disease.
In contrast, importance has previously been poorly attached to tau protein as a target for the treatment of Alzheimer's disease and the like; however, the tau protein is more recently becoming a target for the treatment of, and a vaccine for, tauopathy accompanied by the excess accumulation of the tau protein, as a target for a therapeutic agent for Alzheimer's disease (Non Patent Literature 7).
Reported therapeutic agents related to the present invention include therapeutic agents for Alzheimer disease, in which an adeno-associated viruscarried a gene encoding amyloid (Patent Literatures 1 and 2 and Non Patent Literature 8), and methods for treating Alzheimer disease and tauopathy by inoculating tau protein (Patent Literature 3 and Non Patent Literature 9); however, the effects of improving coordinated movement and motor learning were observed in tauopathy model mice inoculated with tau protein but there were not observed the effects of improving the symptoms characteristically seen in dementia patients of unsociability and reduced recent memory.